Bone marrow mesenchymal stem cell–derived exosomes alleviate high phosphorus-induced vascular smooth muscle cells calcification by modifying microRNA profiles
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Vascular calcification is a common complication in patients with chronic kidney disease (CKD). It is an important predictor of cardiovascular disease and all-cause mortality. Previous studies have confirmed that bone marrow mesenchymal stem cell (BMSC) therapy can reduce vascular calcification, but the specific mechanism is still controversial. In this study, we aimed to investigate the mechanisms of BMSC-derived exosomes (EXO) in improving vascular calcification. BMSCs were cultured and EXO were isolated using the Total Exosome Isolation Reagent. Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured into three groups: control group, high phosphorus group, and high phosphorus plus EXO group. Then, indicators related to smooth muscle cell calcification and microRNA profiles were analyzed. BMSC-derived exosomes inhibited high phosphorus-induced calcification in HA-VSMCs. Besides, EXO treatment reduced calcium content and decreased the alkaline phosphatase (AKP) activity in high phosphorus co-incubated HA-VSMCs. MicroRNA (miRNA) and mRNA expression profiles analyses revealed that 63 miRNAs were significantly upregulated and 1424 genes were significantly downregulated in HA-VSMCs after EXO treatment. Functional miRNA-gene regulatory network revealed that mTOR, MAPK, and Wnt signaling pathway were involved in vascular calcification. BMSC-derived exosomes alleviated high phosphorus-induced calcification in HA-VSMC through modifying miRNA profiles.
KeywordsChronic kidney disease Vascular calcification Exosomes Bone mesenchymal stem cells MicroRNA
We also thank Clare Cox, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript. We would especially like to thank Dr. Wei Chen (Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University) for helpful suggestions and revisions.
The authors wish to thank the Beijing Talents Fund (No. 2016000021469G223), the National Natural Science Foundation of China (No. 81570660), and the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201824) for financial support.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
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